Capsaicin desensitization protects from antigen-induced bronchospasm in conscious guinea-pigs.
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Anaphylaxis↗
Biomedical subjects
P Geppetti
Publications and source records attributed to P Geppetti.
The correlation between sensory-efferent functions mediated by the capsaicin-sensitive neurons and substance P content of the rat urinary bladder.
The substance P-like immunoreactivity (SP-LI) of the urinary bladder of adult rats was depleted by capsaicin desensitization (50 mg/kg, s.c., 4 days before) or extrinsic denervation (pelvic ganglionectomy) thus indicating its neurogenic sensory origin. SP-LI levels were inversely proportional to the volume threshold for micturition but not to the amplitude of micturition contraction. Moreover SP-LI levels were directly related to the amplitude of the capsaicin- but not field stimulation-induced contraction of the rat isolated bladder. These findings indicate that the SP-LI level of the rat bladder is a useful index for monitoring the dual sensory-efferent functions of the capsaicin-sensitive innervation of this organ.
Animals↗
Cutaneous lesions in capsaicin-pretreated rats. A trophic role of capsaicin-sensitive afferents?
1. The time course and regional distribution of 'spontaneous' cutaneous lesions in rats desensitized to capsaicin as newborns was correlated to behavioural observations and regional distribution of substance P-like immunoreactivity (SP-LI) and tachykinin-like immunoreactivity (TK-LI) in various skin areas. 2. 'Spontaneous' skin lesions in the form of wounds, scabs and areas of alopecia were observed in 80-90% of rats desensitized to capsaicin. No major sex-related differences were observed with regard to incidence and distribution of the lesions with the possible exception of a lesser tendency to bilateral lesions in female rats. 3. 'Spontaneous' skin lesions were almost restricted to the head: the areas most frequently affected were snouts, periocular and retroauricular regions and ventral area of the neck. 4. No major differences were observed between capsaicin- or vehicle-treated animals in spontaneous or novelty-induced grooming as well as in open-field gross behaviour. Likewise, no differences were observed in the mouse-killing behaviour. 5. Both SP-LI and TK-LI in various skin areas were significantly reduced by systemic capsaicin pretreatment. The rank order of various skin areas for SP-LI or TK-LI levels was: snouts greater than thigh greater than neck greater than abdomen approximately equal to retroauricular region. 6. Intradermal injection of Arg-neurokinin B, a potent and water soluble derivative of neurokinin B, produced a similar plasma extravasation (Evans blue leakage technique) in the skin of vehicle- or capsaicin-pretreated rats. 7. In capsaicin-desensitized rats fur regrowth (measured at abdominal level, 28 days after shaving) was significantly less than in vehicle-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Species-related variations in the effects of capsaicin on urinary bladder functions: relation to bladder content of substance P-like immunoreactivity.
1. The effect of capsaicin on bladder motility in vivo (urethane anaesthesia) and in vitro, plasma extravasation (Evans blue leakage technique) and content of substance P-like immunoreactivity (SP-LI) of the urinary bladder was investigated in various mammalian species. 2. Systemic capsaicin desensitization (rat and hamster, 50 mg/kg s.c. 4 days before; guinea-pig 55 mg/kg s.c. 4-7 days before) increased bladder capacity in rats and guinea-pigs and reduced voiding efficiency in guinea-pigs. All other urodynamic parameters were unaffected in both rats, guinea-pigs and hamsters. 3. Reflex bladder voiding was abolished by spinal cord transection in anaesthetized rats and hamsters. On the other hand, hexamethonium-(20 mg/kg i.v.)sensitive voiding contractions were obtained in response to saline filling 45 min from cord transection in guinea-pigs, indicating a profound interspecies variation in the basic organization of micturition. 4. Exposure to capsaicin (1 microM) produced a contraction of the isolated bladder from rats, guinea-pigs (dome) and mice. Capsaicin produced only a slight contractile response in the guinea-pig bladder base. The motor response to capsaicin of the rat, guinea-pig and mouse bladder exhibited marked desensitization, suggesting a specific effect on sensory nerves. On the other hand, capsaicin (1 microM) produced a slight relaxation of the hamster isolated bladder but this effect was reproducible at 1-2 h intervals, suggesting an unspecific effect. Capsaicin (1-10 microM) did not affect motility of strips from the dome or the base of the rabbit bladder. 5. Intravenously administered capsaicin produced a marked plasma extravasation (Evans blue leakage) in the lower urinary tract of rats, mice and guinea pigs. In rats but not guinea-pigs the reaction in the bladder base was greater than in the dome. In hamsters intravenous capsaicin failed to induce any significant Evans blue leakage in the lower urinary tract. 6. SP-LI was detected in the lower urinary tract of rats, guinea-pigs, rabbits and mice but not hamsters. Bladder SP-LI was depleted by systemic capsaicin desensitization in rats, guinea-pigs and mice. Reverse phase HPLC indicated that all the immunoreactive material co-eluted with authentic substance P or its oxidized form. 7. These findings indicate that noticeable species-related differences exist with regard to the functions mediated by the capsaicin-sensitive neurons in the urinary bladder.
Animals↗
Vasoactive intestinal polypeptide levels and distribution in the penis of old rats.
Vasoactive intestinal polypeptide (VIP) levels and distribution were studied in the penis of young-adult (3-month-old) and old (30-month-old) Wistar rats by radioimmunoassay and immunofluorescence. No significant changes in tissue VIP concentrations or distribution occurred in the penis of old rats compared to young-adult rats. The present data indicate that the age-related impairment of male sexual function is not dependent on modifications of the VIP-ergic innervation of penile tissue.
Aging↗
Substance P-like immunoreactivity in capsaicin-sensitive structures of the rat thymus.
Unlike in mouse and hamster, the thymus of rats or guinea pigs contains measurable amounts of substance P-like immunoreactivity (SP-LI), which, in a HPLC system, eluted as authentic SP or SP sulfoxide. Ontogenetic study showed that in rats the SP-LI content of the thymus increased up to 60 days from birth, and decreased thereafter. Capsaicin, but not 6-hydroxydopamine (6-OHDA) pretreatment completely depleted thymic SP-LI content in both newborn and adult rats. Animals treated with capsaicin as newborns, but not as adults, showed lower thymus weights as compared to controls. Rats pretreated with capsaicin as adults underwent partial time-dependent recovery of thymic SP-LI content. Somatostatin-like immunoreactivity (SST-LI) of rat thymus, eluting in part as authentic SST, was unaffected both by capsaicin or 6-OHDA pretreatment. Taken together, these findings demonstrate the existence of capsaicin-sensitive structures containing SP in the rat thymus. The possible function(s) that capsaicin-sensitive structures could exert in the thymus, among which a trophic action, mediated by the efferent function of sensory neurons, remain(s) to be established.
Aging↗
Acute oral captopril inhibits angiotensin converting enzyme activity in human cerebrospinal fluid.
Angiotensin converting enzyme (ACE) activity in human plasma and cerebrospinal fluid (CSF), was measured by a fluorimetric method, following an acute oral dose (75 mg) of captopril. A decrease of approximately 60% in enzyme activity was observed in CSF, suggesting that the drug penetrates the blood/brain barrier (BBB) in sufficient amounts to inhibit the ACE in CSF. The activity of CSF enkephalinase, an enzyme present in human brain and inhibited in vitro by an elevated concentration of captopril, was, however, unaffected by the acute drug administration. It is proposed that the antihypertensive effect of captopril in humans may be due, at least in part, to the inhibition of ACE contained within brain structures.
Administration, Oral↗
Evaluation of CSF neuropeptides and peptidase activities in primary headaches.
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Adult↗
In vivo 'enkephalinase' inhibition by acetorphan in human plasma and CSF.
Thiorphan, the potent inhibitor of 'enkephalinase', has shown some analgesic properties in experimental animals and in man. The possibility that the intravenous infusion of acetorphan, a prodrug of thiorphan (26 micrograms/kg per min for 60 min), can inhibit plasma and cerebrospinal fluid (CSF) enkephalinase in man in vivo was investigated. A decrease of approximately 65% in enzyme activity was observed in both plasma and CSF. Acetorphan did not induce any significant variation of plasma angiotensin-converting enzyme activity.
Amino Acids, Sulfur↗
Substance P and enkephalins: a creditable tandem in the pathophysiology of cluster headache and migraine.
Substance P, present in primary sensory neurones, seems to take part in nociceptive transmission within the trigeminal system. Substance P, released by peripheral axons of these neurones, induces vasodilatation, plasma extravasation, miosis, conjunctival and nasal congestion. All these effects bear some similarity to symptoms of cluster headache and migraine attack. Opiates and somatostatin inhibit the release of substance P from primary sensory neurones and relieve both pain and autonomic symptoms of cluster headache attack. Plasma substance P-like immunoreactivity was decreased during spontaneous attack of cluster headache and migraine and during histamine precipitated attack of cluster headache. Taken together these data suggest that substance P and endogenous opioids could be implicated in the pathophysiology of cluster headache and migraine.
Analgesia↗
Effect of verapamil on catecholamine secretion by human pheochromocytoma.
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Adrenal Gland Neoplasms↗
Characterization of [3H]5-hydroxytryptamine uptake within rat cerebrovascular tree.
The in vitro uptake of tritiated serotonin ([3H]5HT) was studied in a preparation of rat extracerebral arteries. The uptake of [3H]5HT was time- and temperature-dependent and of high affinity; linear regression analysis gave a Km value of 6.48 X 10(-7) M for the specific uptake. Bilateral superior cervical ganglionectomy was without effect on [3H]5HT uptake while it significantly reduced the uptake of tritiated norepinephrine by the preparation of rat extracerebral arteries. The serotonergic neurotoxin 5,7-dihydroxytryptamine and lesions to both the medial and the dorsal raphe nuclei caused a marked loss of [3H]5HT uptake but did not change the uptake of tritiated norepinephrine. Competition studies with norepinephrine, desimipramine (a noradrenergic uptake blocker), nomifensine (a dopaminergic uptake blocker) and fluoxetine (a 5HT uptake blocker) confirmed the specificity of the [3H]5HT uptake mechanism. Histoautoradiographic studies showed the highest density of silver grains at the level of the adventitial-medial border of the basilar artery. Fluoxetine inhibited the accumulation of silver grains within the adventitial-medial border in the blood vessel studied. The present data further support the view that a neuronal serotonergic system may play a role in the control of blood flow in the cerebrovascular tree.
5,7-Dihydroxytryptamine↗
Substance P mechanism in cluster headache: evaluation in plasma and cerebrospinal fluid.
Substance P (SP), present in sensory afferent neurons, seems to process nociceptive information in the trigeminal system. SP, released from peripheral trigeminal endings, causes typical cluster headache (CH) signs, e.g. vasodilatation, conjunctival and nasal edema and miosis. Opiates and somatostatin (SRIF), both active in relieving CH attack, inhibit SP release from the central and peripheral trigeminal system. In the present study, plasma and cerebrospinal fluid (CSF), SP-like immunoreactivity (SPLI) and enkephalinase activity (EKA), and plasma SRIF-like immunoreactivity (SRIFLI) have been evaluated during spontaneous and histamine induced attacks in the cluster phase. During the histamine provoked attacks, CSF SPLI and plasma SRIFLI and EKA were unchanged, while plasma SPLI decreased significantly. During spontaneously occurring attacks, plasma SRIFLI was found to be unmodified and a significant lowering of SPLI was detected when compared with controls. Moreover, both during and between attacks in the cluster phase, plasma EKA was increased in comparison with the values in controls. It remains to be seen whether variations of plasma SPLI and EKA levels play a role in the CH mechanism.
Adult↗
Pain relief by somatostatin in attacks of cluster headache.
The pain relieving effect of somatostatin treatment during 72 attacks of cluster headache in 8 male patients was compared to treatment with ergotamine or placebo in a double-blind study. Infusion of somatostatin (25 micrograms/min for 20 min i.v.) reduced the maximal pain intensity and the duration of pain significantly compared to placebo treatment, and to a degree comparable to ergotamine tartrate treatment (250 micrograms i.m.). The results obtained provide new information concerning the possible mechanism of cluster headache attacks and suggest a new therapeutic approach.
Adult↗
Substance P and endogenous opioids: how and where they could play a role in cluster headache.
Substance P appears to be involved in the transmission of pain signals from the periphery to the spinal cord and brain stem. Substance P containing neurons are responsible for the neurogenic vasodilation identical to that obtained by substance P release evoked by antidromic stimulation of these fibres. Both endogenous opioids and somatostatin inhibit the release of substance P from central and peripheral endings. Present pharmacological investigations conclude that morphine and somatostatin are as effective as ergotamine in reducing the pain of CH. All three drugs are significantly more active than placebo. Somatostatin and opiates could act by inhibiting the release of substance P.
Adult↗
Age-related changes in substance P and vasoactive intestinal polypeptide immunoreactivity in the rat stomach and small intestine.
Immunoreactivity for substance P (SP-LI) and vasoactive intestinal polypeptide (VIP-LI) in the stomach, duodenum, jejunum and ileum of young (3-month-old), adult (12-month-old) and old (28-month-old) male Wistar rats were determined by radioimmunoassay. SP-LI and VIP-LI did not show changes in the stomach or in the small intestine portions investigated in adult in comparison with young rats. In old rats SP-LI levels were unchanged in the stomach and in the duodenum, reduced in the jejunum and increased in the ileum. VIP-LI concentrations were unchanged in the stomach, and remarkably reduced in the duodenum, jejunum and ileum of old rats. Since the two neuropeptides investigated are localized primarily within different intrinsic gastrointestinal neurons, the present findings suggest that the various populations of gastrointestinal neurons are affected in a different manner during aging.
Journal Article↗
NK1 receptor antagonist CP-99,994 inhibits cigarette smoke-induced neutrophil and eosinophil adhesion in rat tracheal venules.
The involvement of neurokinin NK1 receptors in cigarette-induced adhesion of neutrophils and eosinophils to venules of the airway mucosa was investigated. Rats were pretreated with the NK1 receptor antagonist CP-99,994 (4 mg/kg IV), its vehicle, or its inactive enantiomer CP-100,263 before exposure to cigarette smoke. Adherent neutrophils and eosinophils were stained histochemically for endogenous peroxidase activity and were counted in tracheal whole mounts. Plasma leakage was quantified be stereological measurements of the extravasation of Monastral blue. Cigarette smoke induced the adhesion of 104 + 17 neutrophils and 10.4 +/- 1.7 eosinophils per square millimeter of mucosa. CP-99,994 reduced neutrophil and eosinophil adhesion by 66 and 61%, respectively, and reduced plasma extravasation by 61% (p < .05), but CP-100,263 had no significant effect. The inhibitory effects of CP-99,994 appeared to be specific because CP-99,994 had no effect on neutrophil and eosinophil adhesion, or on plasma extravasation induced by platelet activating factor, an inflammatory stimulus acting independently of NK1 receptors. These results suggest that NK1 receptors are involved in cigarette smoke-induced adhesion of neutrophils and eosinophils to the endothelium of venules in the rat tracheal mucosa.
Animals↗